The intervertebral disc resides between the vertebral bodies of the spine and provides support for spinal load as well as allowing for relative motion between adjacent vertebral bodies. Degeneration of the intervertebral disc is a multi-factor process that leads to pain and temporary or even permanent disability. The economic consequence of intervertebral degeneration has been estimated at $7.6 billion for a single year in the United States alone.
The intervertebral disc includes two distinct regions (FIG. 1) including the nucleus pulposus 2 and the annulus fibrosus 4. Intervertebral disc degeneration is generally initiated within the nucleus pulposus 2, which is formed of a resilient and hydrophilic hydrogel, comprised primarily of collagen type II fibrils randomly oriented within a glycosaminoglycan matrix. Elastin molecules have also been shown to be present in the human nucleus pulposus, and are believed to play a role in aiding the restoration of intervertebral disc matrix deformation. The annulus fibrosus 4 is formed of reinforcing sheets of type I collagen surrounding the nucleus pulposus 2.
Depending upon the nature and severity of the degeneration, treatment options can range from physical therapy or chiropractic treatment, often in conjunction with anti-inflammatory medications, to spinal fusion, in which the intervertebral disc can be completely removed, with many additional options of various severities between the two. Recently, treatment options have been extended to include nucleus pulposus replacement, which can be an option for early stage intervention to remove the source of the degeneration and associated pain without the necessity of spinal fusion.
One difficulty with advancing nucleus pulposus replacement as a viable treatment option has been finding a mimetic surrogate material that can meet both surgical and implant requirements. For instance, the ideal material would be one that could be implanted according to a process that is not overly invasive, e.g., by injection or other minimally invasive procedure. In addition, the ideal material would be tailorable to individual patient anatomy and could provide the necessary mechanical properties while supporting ingrowth of natural tissue so as to regenerate healthy host tissue.
Progress has been made toward developing possible nucleus pulposus replacement materials. For instance, investigators have shown that biomaterials made of soluble elastin-like peptide sequences can promote the differentiation of adult stem cells into a phenotype similar to that of a nucleus pulposus cell, without the use of exogenous supplements and in a low oxygen environment reminiscent of the nucleus pulposus. Injectable biomaterials comprised of elastin have also been developed. Another group has developed and evaluated a chemically modified hyaluronan-elastin-like peptide composite hydrogel for use as a scaffold for nucleus pulposus tissue engineering. Results include improved mechanical properties compared to previous materials, such as gels composed of hyaluronan alone, as well as improved maintenance of human nucleus pulposus cell viability and phenotype over a culture period (e.g., three weeks). In another study, a recombinant protein copolymer of silk and elastin produced by genetically modified E. coli bacteria, known as the NuCore Injectable Nucleus (Spine Wave, Inc.), has shown promise for use as a cell delivery vehicle. Other studies have illustrated the benefit of glycosaminoglycan-based hydrogels when utilized as nucleus pulposus scaffolds with respect to the maintenance of nucleus pulposus cell viability and phenotype.
Despite such progress, room for improvement in the development of a nucleus pulposus replacement material exists. For instance, problems still exist with materials developed to date such as the need for invasive delivery procedures, the inability to encourage regeneration of healthy host tissue, weak mechanical properties following implant, incomplete in situ curing for injectable materials, the utilization of toxic crosslinking agents, and the possibility of wear debris generation following implant.
Accordingly, what is needed in the art is a viable candidate for use as nucleus pulposus replacement material as well as for use as a scaffold for nucleus pulposus tissue engineering.